Melatonin is a methoxyindole synthesized in retinal and pineal gland. In retina, melatonin synthesis occurs primarily in photoreceptors. Retinal melatonin is involved in the regulation of cellular function of photoreceptors retinal pigment epithelial cells, and dopamine neurons. Dopamine regulates melatonin biosynthesis and also directly influences photoreceptor function. A homeostatic relationship between dopamine and melatonin may play a vital role in the circadian or photoperiodic regulation of visual cell functions, such as outer segment membrane turnover. The long-term goal of the study is to characterize the melatonin system of retina and related aspects of visual cell physiology. To this end, cellular and intercellular mechanisms in the regulation of melatonin synthesis and retinal actions will be explored. Specifically, experiments will be conducted (1) to determine the biochemical basis for the coupling of calcium channel activity to cyclic AMP accumulation and melatonin synthesis in photoreceptor cells, (2) to investigate the roles of neurotransmitters in she regulation of melatonin synthesis by light and circadian oscillators, and (3) to investigate the cellular mechanisms for melatonin's actions in the retina, primarily by characterizing the effects of melatonin receptor activation on second messenger systems. These studies involve the use of cell and tissue culture, neuropharmacological, and biochemical methodologies. The research is significant because it will characterize cellular and biochemical systems that play an important role in the regulation of retinal physiology. It is anticipated that characterization of these systems will contribute to the understanding of visual cell physiology and the pathological processes that underlie photoreceptor degeneration.